Professor, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong.  Research interests: biology and clinical applications of distraction histogenesis and stem cells.  He has published more than 300 papers in journals such as Biomaterials, Nature Communications, Advanced Science, Bioactive Materials, etc., 15 monographs, and edited 2 books. His papers have been cited more than 21,000 times, H index 76.  He is the Executive deputy editor-in-chief of Journal of Orthopedic Translation, editorial board member of Bone and Joint Research, Bone, Journal of Orthopedic Research, etc. He is a visiting professor at Monash Australia; University of Science Malaysia, Nanjing Medical University, etc.  His work received serval awards including 1st Class Award in Science Advances, Ministry of Science and Technology, PR China (2021); 2nd Class Award in Medical Science and Technology, China Medical Association (2017); 1st Class Research Award in Science and Technology, Ministry of Education, China (2014). He is elected as Fellow of International Combined Orthopaedic Research Societies (FIORS) in 2016 and Fellow of American Orthopaedic Research Society (FORS) in 2021.  From 2020 to present, he has been on the list of the world's top 2% scientists (ranked among the 1% of the world's top scientists in 2022 and 2023). In 2023, he is ranked 9th of the top 100 scholars in the field of orthopedic surgery in PR China.  

Topic title: Bioreactor derived human fetal mesenchymal stem cell secretome promote diabetic skin wound healing

Abstract:

INTRODUCTION: Fetal tissue usually heals in a scar-less manner. Our study makes use of bioreactor expended human fetal mesenchymal stem cell (FMSC) to produce MSC secretome (HFS) in large scale. We prove the promoting effect of HFS encapsulated poly (lactic-co-glycolic acid) particle (HEP) on the healing of diabetic skin wound which is considered as a refractory defect in clinical.

METHOD: FMSC were seeded on collagen-coated polystyrene microcarrier in the ratio of one million cells/30g carriers in the bioreactor. Upon collection of HFS, cultures were incubated with serum-free medium for 24hrs. Collected medium was filtered with 70μm cell strainer (Falcon) and removed the cell debris by centrifugation. The supernatant was subjected to lyophilization. Alamar blue (Invitrogen) was used to test cell viability. Scratch assay and co-culture insertion (BD Bioscience) was used to test cell migration ability. Furthermore, fibroblast populated collagen lattice (FPCL) model and organotypic keratinocyte-fibroblast co-culture (OKC) system were used to test the effect of HEP in vitro. For in vivo study, we employed streptozotocin-induced diabetes model in rat and created a full thickness defect on rat back skin.

RESULTS: FMSC is mixed with microcarrier and cultured under stirring within bioreactor for 14 days. Alamar blue test shows that 50ng/mL HFS promote human fibroblast and keratinocyte viability (n=3, P<0.05). HFS also promote cell migration of two types of human cells, fibroblast, and keratinocyte, after treatment for 3days (n=3, P<0.05). Simultaneously, HFS prohibit FPCL contraction and promote keratinocyte differentiation in the OKC model after 7 days treatment (n=3, P<0.05). Then HFS was encapsulated in PLGA particle by double emulation method. ELSA data shows that HFS contains PDGF-BB. The promoting effect has also been observed on the diabetic rat model (n=6, P<0.05). HFS also contains long non-coding RNA H19 which may contribute to skin healing.

DISCUSSION: In summary, HFS  encapsulated particles is more efficient in promoting diabetic wound healing. PDGF-BB and H19 in HFS may be novel targets for promoting diabetic skin wound healing.